Recognizing that cartilage degradation is an expected consequence of inflammatory and degenerative joint disease and that the proteoglycan and cellular constituents comprising cartilage matrix are antigenic, it is proposed to examine the potential immunopathologic significance of such cartilage componentr as regards the causation and/or perpetuation of joint inflammation and cartilage destruction. Both antibody and cell mediated immune response to purified proteoglycans and chondrocytes and their synthetic products derived from human articular cartilage are to be evaluated. Patients manifesting overt inflammatory joint disorders such as rheumatoid arthritis, gout, Reiter's disease, psoriatic arthropathy and infectious arthritis as well as basically non-inflammatory entities such as degenerative joint disease will be studied. Earlier investigations in this laboratory are to be extended to assess the capacity of lymphocytes sensitized to such antigens to liberate factors capable of curtailing chondrocyte synthesis of proteoglycans as well as facilitating depletion of matrix. It is also proposed to use laboratory models of inflammatory joint disease and degenerative arthritis in order to sequentially determine potential immunopathologic events related to structural alteration in cartilage and perpetuation of existent inflammation.